(R)-4-amino-3-(4-chlorophenyl)butanoic acid ((R)-(−)-baclofen) is a compound which is useful as a reflux esophagitis remedy or antispasmodic. There are known several methods for synthesizing this compound and, for example, Journal of the American Chemical Society, 2005, vol. 127, p. 119-125 (hereinafter, described as non-patent document 1 in some cases) discloses the following method as a method of efficiently synthesizing the compound.

Further, Journal of the American Chemical Society, 2005, vol. 127, p. 9958-9959, Journal of the American Chemical Society, 2004, vol. 126, p. 11148-11149 and Journal of the American Chemical Society, 2004, vol. 126, p. 9906-9907 (hereinafter, described as non-patent document 2, non-patent document 3 and non-patent document 4, respectively, in some cases) disclose production of optically active 2-(1-substituted phenyl-2-nitroethyl)malonic acid diesters typified by diethyl (R)-2-(1-(4-chlorophenyl)-2-nitroethyl)malonate (4) by asymmetric Michael addition of a malonic acid diester to β-nitrostyrenes typified by 4-chloro-β-nitrostyrene (3) using various asymmetric catalysts.
These β-nitrostyrenes and 2-(1-substituted phenyl-2-nitroethyl)malonic acid diesters are dangerous compounds having a fear of explosion because of a nitro group in them. Particularly, β-nitrostyrenes are compounds having a high possibility of explosion since they have a double bond conjugating a nitro group. Therefore, drying these compounds isolated is problematical in point of safety, and accompanied by a danger particularly in production on industrial scale.
Journal of the American Chemical Society, 2002, vol. 124, p. 13097-13105 (hereinafter, described as non-patent document 5 in some cases) discloses a method of producing β-nitrostyrenes, and here, benzaldehydes are reacted with ammonium acetate and nitromethane in acetic acid, then, the deposited crystal is filtrated, washed with water and dried, to obtain β-nitrostyrenes. This method obtains β-nitrostyrenes directly from benzaldehydes, thus, this method shows a shorter process as compared with a method of obtaining 4-chloro-□-nitrostyrene (3) from 4-chlorobenzaldehyde (1) via 4-chloro-α-nitromethylbenzyl alcohol (2) as in the method of the non-patent document 1, and since solvent extraction and the like are not included, this method is an industrially advantageous method. However, in this method, the resultant crystal of β-nitrostyrenes is one finally water-washed, namely, the resultant crystal contains a considerable amount of water, and it is necessary to dry this crystal sufficiently before being subjected to the subsequent process. In this case, however, there is a high danger of explosion and the like as described above, and particularly in production on industrial scale, its safety problem possibly generates a non-applicable disturbance.
In the non-patent document 1, non-patent document 2, non-patent document 3, non-patent document 4 and patent document 1, 2-(1-substituted phenyl-2-nitroethyl)malonic acid diesters are isolated as crystal and dried, however, drying of this compound also inevitably produces a safety problem because of the reason described above.
JPS45-16692B (hereinafter, described as patent document 2 in some cases) discloses a method in which 4-substituted phenyl-2-oxopyrrolidine-3-carboxylic acid esters typified by 4-(4-chlorophenyl)-2-oxopyrrolidine-3-carboxylate ethyl (5) are added to a mineral acid such as hydrochloric acid and the like and the mixture are heated under reflux, to obtain 4-amino-3-substituted phenylbutanoic acids typified by 4-amino-3-(4-chlorophenyl)butanoic acid (7). This method is an industrially advantageous method due to fewer processes since this method is carried out not via 4-substituted phenylpyrrolidin-2-ones typified by 4-(4-chlorophenyl)-pyrrolidin-2-one (6) as in the non-patent document 1. In this method, carbon dioxide is generated, and in the method of adding 4-substituted phenyl-2-oxopyrrolidine-3-carboxylic acid esters as they are to a mineral acid as in the patent document 2, control of carbon dioxide to be generated is difficult, and in some cases, there is a possibility of generation of carbon dioxide at one time, leading to a strict problem in production on industrial scale.